Chinese patent medicine combined with calcium channel blockers in the treatment of essential hypertension:a Bayes network meta-analysis and systematic review.

Backgroud: The co-administration of Chinese patent medicine with calcium channel blockers (CCBs) is a prevalent practice in China for treating essential hypertension (EH). However, robust evidence supporting the efficacy and safety of tailored combinations of different Chinese patent medicines with CCBs, according to individual patient conditions, is still limited. This study sought to elucidate the efficacy and safety of these combinations using a systematic review and network meta-analysis. Materials and methods: Relevant studies were sourced from established databases, incorporating randomized controlled trials published up to 1 February 2023. The ROB2 tool from the Cochrane Collaborative Network was employed to independently assess and cross-verify the quality of the included literature. A network meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 and PRISMA-Network Meta-Analyses (PRISMA-NMA) guidelines. A Bayesian network meta-analysis was utilized to gauge the efficacy and safety of distinct integrations of Chinese patent medicine and CCBs. Primary outcomes were interpreted using a paired fixed-effect meta-analysis. Publication bias was appraised through Egger's test and represented with funnel plots. All statistical analyses were executed within the R statistical framework. Results: Following rigorous selection, data extraction, and bias evaluation, 36 articles were incorporated. Tianma Gouteng Granule, when combined with CCBs, displayed superior efficacy in reducing systolic blood pressure (SBP). In terms of diastolic blood pressure (DBP) reduction, Songling Xuemaikang Capsule combined with CCBs emerged as the most effective. Regarding enhancement of antihypertensive effective rates, Qinggan Jiangya Capsule paired with CCBs demonstrated optimal results. For diminishing Traditional Chinese Medicine syndrome scores, the Qiangli Dingxuan Tablet and CCBs combination proved most beneficial. When aiming to reduce total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) levels, Tianma Gouteng Granule and CCBs showcased superior results. In contrast, the combination of Songling Xuemaikang Capsule and CCBs was more effective in reducing LDL-C, tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6). Conclusion: This study underscores variability in outcomes from combining Chinese patent medicine and CCBs for hypertension, emphasizing the importance of personalized medicinal combinations, especially Tianma Gouteng Granule and Songling Xuemaikang Capsule. The results offer robust evidence to inform clinical guidelines for essential hypertention and significantly aid clinician in seleting appropriate Chinese patent medicines for treatment.

Elucidating the anti-hypertensive mechanisms of Uncaria rhynchophylla-Alisma plantago-aquatica L: an integrated network pharmacology, cluster analysis, and molecular docking approach.

Background: With the increasing global prevalence of hypertension, a condition that can severely affect multiple organs, there is a growing need for effective treatment options. Uncaria rhynchophylla-Alisma plantago-aquatica L. (UR-AP) is a traditional drug pair used for treating hypertension based on the liver-kidney synergy concept. However, the detailed molecular mechanisms underlying its efficacy remain unclear. Methods: This study utilized an integrative approach combining network pharmacology, cluster analysis, and molecular docking to uncover the bioactive components and targets of UR-AP in the treatment of hypertension. Initially, we extracted data from public databases to identify these components and targets. A Protein-Protein Interaction (PPI) network was constructed, followed by enrichment analysis to pinpoint the bioactive components, core targets, and pivotal pathways. Cluster analysis helped in identifying key sub-networks and hypothesizing primary targets. Furthermore, molecular docking was conducted to validate the interaction between the core targets and major bioactive components, thus confirming their potential efficacy in hypertension treatment. Results: Network pharmacological analysis identified 58 bioactive compounds in UR-AP, notably quercetin, kaempferol, beta-sitosterol (from Uncaria rhynchophylla), and Alisol B, alisol B 23-acetate (from Alisma plantago-aquatica L.), as pivotal bioactives. We pinpointed 143 targets common to both UR-AP and hypertension, highlighting MAPK1, IL6, AKT1, VEGFA, EGFR, and TP53 as central targets involved in key pathways like diastolic and endothelial function, anti-atherosclerosis, AGE-RAGE signaling, and calcium signaling. Cluster analysis emphasized IL6, TNF, AKT1, and VEGFA's roles in atherosclerosis and inflammation. Molecular docking confirmed strong interactions between these targets and UR-AP's main bioactives, underscoring their therapeutic potential. Conclusion: This research delineates UR-AP's pharmacological profile in hypertension treatment, linking traditional medicine with modern pharmacology. It highlights key bioactive components and their interactions with principal targets, suggesting UR-AP's potential as a novel therapeutic option for hypertension. The evidence from molecular docking studies supports these interactions, indicating the relevance of these components in affecting hypertension pathways. However, the study acknowledges its limitations, including the reliance on in silico analyses and the need for in vivo validation. These findings pave the way for future clinical research, aiming to integrate traditional medicine insights with contemporary scientific approaches for developing innovative hypertension therapies.

Soil organic carbon stability mediate soil phosphorus in greenhouse vegetable soil by shifting phoD-harboring bacterial communities and keystone taxa.

Addition of organic amendments, such as manure and straw, to arable fields as a partial substitute for mineral phosphorus (P), are a sustainable practice in high-efficiency agricultural production. Different organic inputs may induce varied soil organic carbon (OC) stability and phoD harboring microbes, subsequently regulate P behavior, but the underlying mechanisms are poorly understood. A 11-year field experiment examined P forms by 31P-nuclear magnetic resonance (NMR), OC chemical composition by 13C NMR, and biologically-based P availability methods, phoD bacterial communities, and their co-occurrence in soils amended with chemical P fertilizer (CF), chemical P partly substituted by organic amendments including pig manure (CM), a mixture of pig manure and corn straw (CMS), and corn straw (CS), with equal P input in all treatments. Organic amendments significantly increased soil labile Pi (CaCl2-P, citrate-P, 2.91-3.26 and 1.16-1.32 times higher than CF) and Po (enzyme-P, diesters, 4.08-7.47 and 1.71-2.14 times higher than CF) contents and phosphatase activities, while significantly decreased aromaticity (AI) and recalcitrance indexes (RI) of soil C, compared with CF. The keystone genera in manured soils (Alienimomas and Streptomyces) and straw-applied soils (Janthinobacterium and Caulobacter) were significantly correlated with soil enzyme-P, microbial biomass P (MBP), diesters, and citrate-P. Soil AI and RI were significantly correlated with the phoD keystone and soil P species. It suggested that the keystone was impacted by soil OC stability and play a role in regulating P redistribution in amended soils. This study highlights how manure and straw incorporation altered soil OC stability, shaped the phoD harboring community, and enhanced soil P biological processes promoted by the keystone taxa. The partial substitution of mineral P by mixture of manure and straw is effectively promote soil P availability and beneficial for environmental sustainability.

Integrated manganese (III)-doped nanosystem for optimizing photothermal ablation: Amplifying hyperthermia-induced STING pathway and enhancing antitumor immunity.

Despite the great promise initially demonstrated by photothermal ablation (PTA) therapy, its inability to completely ablate large tumors is problematic, because this has been found to result in residual tumors at ablation margins and bring a relative high rate of subsequent recurrences and metastases. To address this issue, we herein report a smart photothermal nanosystem (PBM) based on FDA-approved Prussian blue (PB) nanoparticles, doped with Mn (III) to suppress the tumor debris left by incomplete ablation. Notably, our study demonstrated that PTA-induced hyperthermia plays a crucial role in initiating the cGAS-STING pathway by generating damaged cytosolic DNA. This PBM nanosystem, which consumes glutathione and continuously releases Mn(II), further amplifies the PTA-induced cGAS-STING pathway in CT26 colon and 4T1 breast tumor models. Moreover, treatment with PBM following PTA boosted the robust immune response in situ and extended to the whole body with a remarkable suppression effect on both local residual and distant tumors. This work, which improves the antitumor efficacy of nonablated areas utilizing hyperthermia-enhanced immune therapy, may therefore provide a promising adjuvant antitumor strategy for the issue of incomplete ablation. STATEMENT OF SIGNIFICANCE: This work discovered, for the first time, that photothermal ablation-induced hyperthermia plays a crucial role in initiating the cGAS-STING pathway. Taking advantage of this finding, we developed a smart photothermal material (PBM) tailored for incomplete tumor ablation. This integrated Mn(III)-doped nanosystem (PBM) demonstrated superior therapeutic benefits due to the thermal ablation process and immune enhancement. As the photothermal ablation-induced cGAS-STING pathway was triggered, the released Mn(III) consumes GSH while continuously transferred to Mn(II), which further amplified STING activation and facilitated a more robust antitumor immunity, thereby remarkably inhibiting both local residual and distant tumors in virtue of the biological changes under thermal ablation.

Storax Attenuates Cardiac Fibrosis following Acute Myocardial Infarction in Rats via Suppression of AT1R-Ankrd1-P53 Signaling Pathway.

Myocardial fibrosis following acute myocardial infarction (AMI) seriously affects the prognosis and survival rate of patients. This study explores the role and regulation mechanism of storax, a commonly used traditional Chinese medicine for treatment of cardiovascular diseases, on myocardial fibrosis and cardiac function. The AMI rat model was established by subcutaneous injection of Isoproterenol hydrochloride (ISO). Storax (0.1, 0.2, 0.4 g/kg) was administered by gavage once/d for 7 days. Electrocardiogram, echocardiography, hemodynamic and cardiac enzyme in AMI rats were measured. HE, Masson, immunofluorescence and TUNEL staining were used to observe the degree of pathological damage, fibrosis and cardiomyocyte apoptosis in myocardial tissue, respectively. Expression of AT1R, CARP and their downstream related apoptotic proteins were detected by WB. The results demonstrated that storax could significantly improve cardiac electrophysiology and function, decrease serum cardiac enzyme activity, reduce type I and III collagen contents to improve fibrosis and alleviate myocardial pathological damage and cardiomyocyte apoptosis. It also found that storax can significantly down-regulate expression of AT1R, Ankrd1, P53, P-p53 (ser 15), Bax and cleaved Caspase-3 and up-regulate expression of Mdm2 and Bcl-2. Taken together, these findings indicated that storax effectively protected cardiomyocytes against myocardial fibrosis and cardiac dysfunction by inhibiting the AT1R-Ankrd1-P53 signaling pathway.

[Mechanism of Huanglian Houpo Decoction in treatment of ulcerative colitis in mice based on brain-gut axis].

Based on the brain-gut axis, the present study investigated the effect of Huanglian Houpo Decoction(HLHPD) in the treatment of ulcerative colitis(UC) and explored the mechanism in the regulation of 5-hydroxytryptamine(5-HT), substance P(SP), and vasoactive intestinal peptide(VIP) using modern technologies and molecular docking. Sixty male C57 BL/6 J mice were randomly divided into a blank control group, a model group, a sulfasalazine(SASP) group, and high-(5.00 g·kg~(-1)), medium-(2.50 g·kg~(-1)), and low-dose(1.25 g·kg~(-1)) HLHPD groups. The UC model was induced by oral administration of water containing 3% dextran sulfate sodium salt(DSS) in mice except those in the blank control group. After HLHPD was administered for 10 days, the mice were sacrificed for sample collection. Morphological changes of colon tissues were observed by HE staining. The expression of 5-HT, SP, VIP, tumor necrosis factor α(TNF-α), interleukin-6(IL-6), and interleukin-1ß(IL-1ß) in the hypothalamus, serum, and colon was determined by the enzyme-linked immunosorbent assay(ELISA). The expression of tryptophan hydroxylase 1(TPH1), SP, and VIP in colon tissues was evaluated by immunohistochemistry. The expression of brain-gut peptide receptors, such as 5-HT3 A, neurokinin receptor 1(NK-1 R), and VIP receptor 1(VPAC1) in colon tissues was investigated by Western blot. The binding affinity of the brain-gut peptide receptors to the main components of HLHPD was analyzed by molecular docking. After HLHPD intervention, UC mice showed increased body weight, reduced DAI score and occult blood, prolonged colon, down-regulated levels of TNF-α, IL-1ß, and IL-6 in colon tissues, and relieved pathological damage in the colon. The VIP levels in the colon were significantly up-regulated in the HLHPD groups. The high-and medium-dose HLHPD could significantly down-regulated SP and 5-HT in colon tissues and 5-HT in the serum, and up-regulated the VIP in the serum. The high-dose HLHPD group could down-regulate 5-HT and up-regulate VIP in the hypothalamus. It is suggested that HLHPD can reverse the levels of brain-gut peptides in UC mice to varying degrees. Correlation analysis results suggested that the expression levels of brain-gut peptides in the hypothalamus, serum, and colon tissues were related to inflammatory factors. Molecular docking results showed that berberine, coptisine, and epiberberine were presumedly the material basis for HLHPD in regulating the levels of 5-HT3 A, NK-1 R, and VPAC1. The main components of HLHPD may reduce colonic inflammation and pathological damage of colon tissues by regulating the activity of brain-gut peptides and their receptors, thereby reducing DSS-induced colitis in mice.

Delayed autumnal leaf senescence following nutrient fertilization results in altered nitrogen resorption.

Increased atmospheric nitrogen (N) deposition could create an imbalance between N and phosphorus (P), which may substantially impact ecosystem functioning. Changes in autumnal phenology (i.e., leaf senescence) and associated leaf nutrient resorption may profoundly impact plant fitness and productivity. However, we know little about how and to what extent nutrient addition affects leaf senescence in tree species, or how changes in senescence may influence resorption. We thus investigated the impacts of N and P addition on leaf senescence and leaf N resorption in 2-year-old larch (Larix principisrupprechtii) seedlings in northern China. Results showed that nutrient addition (i.e., N, P or N + P addition) significantly delayed autumnal leaf senescence, and decreased leaf N resorption efficiency (NRE) and proficiency (NRP), particularly in the N and N + P treatments. Improved leaf N concentrations were correlated with delayed leaf senescence, as indicated by the positive relationship between mature leaf N concentrations and the timing of leaf senescence. Following nutrient addition, larch seedlings shifted toward delayed onset, but more rapid, leaf senescence. Additionally, we observed an initial negative correlation between the timing of leaf senescence and NRE and NRP, followed by a positive correlation, indicating delayed and less efficient remobilization during the early stages of senescence, followed by accelerated resorption in the later stages. However, the latter effect was potentially impaired by the increased risk of early autumn frost damage, thus failed to fully compensate for the negative effects observed during the early stages of senescence. Improved soil P availability increased leaf N resorption and thus weakened the negative impact of delayed leaf senescence on leaf N resorption, so P addition had no significant impact on leaf N resorption. Overall, our findings clarify the relationship between nutrient addition-resorption and the linkage with leaf senescence, and would have important implications for plant nutrient conservation strategy and nutrient cycling.

Enhanced phosphorus mobility in a calcareous soil with organic amendments additions: Insights from a long term study with equal phosphorus input.

The agricultural practice of replacing chemical fertilizers with organic amendments (manure and/or straw) may have consequences for phosphorus (P) loss to the environment. Such a knowledge gap was examined using a ten-year field trial in calcareous soil containing four treatments with the equal annual P input but varied organic amendment combinations as follows: mineral fertilizer only as control (MF), mineral fertilizer coupled with manure (MM), mineral fertilizer coupled with manure and straw (MMS) and mineral fertilizer coupled with straw (MS). The soil P distribution, P fractions and speciation, Fe(III) reduction and P sorption kinetics were investigated using the chemical extraction, K edge X-ray absorption near-edge structure and Langmuir equations. The electronic shuttle capacity of soils and speciation of soil dissolved organic matter (DOM) were also evaluated using electrochemical methods, three-dimensional excitation-emission matrix fluorescence spectroscopy and Fourier transform infrared spectra methods. Results showed that soil Olsen-P and total P increased at depths of 20-40 cm in MM, MMS and MS treatments, suggesting that manure and/or straw addition significantly mobilized P in the soil profile. Manure and/or straw addition also decreased soil maximum P sorption capacity (Smax) and increased the desorption rate at depths of 0-20 cm in soil across treatments. At a depth of 0-20 cm in soil of the MS treatment, the enhanced Fe(Ⅲ) reduction coupled with a decrease of Fe-bound P supports that Fe reduction dominates the mobilization of P. The transformation of Ca bound-P to Al/Fe bound-P in a depth of 0-20 cm in soil of the MM treatment may be due to the high proportion of humic-like substances in the DOM at a depth of 0-20 cm in soil of the MM treatment, which may have caused a slight/microsite acidification. These results can help to develop optimized fertilization practices to effectively mitigate P loss from calcareous soils with manure and/or straw addition.

Treatment of Psoriasis Vulgaris with Medicated Thread Moxibustion of Zhuang Medicine: A Multicenter Randomized, Parallel Controlled Trial.

OBJECTIVE: To explore the efficacy and safety of Zhuang medicine medicated thread moxibustion (ZMTM) on psoriasis vulgaris. METHODS: A multicenter, randomized, parallel controlled clinical trial was designed. A total of 241 outpatients with psoriasis vulgaris were randomly divided into a control group (120 cases) and a treatment group (121 cases) using a central block randomization from June 2015 to May 2018. The control group was treated with Western medicines alone including pidotimod dispersible tablets, vitamin B compound tablets, and compound cod liver oil-zinc oxide ointment. The treatment group was treated with ZMTM every 2 days combined with Western medicines. The two groups received continuous intervention for 30 days. The primary outcome was Psoriasis Area and Severity Index (PASI), and the secondary outcomes included Itch Rating Scale, Dermatology Quality of Life Index (DLQI), Hamilton Anxiety Rating Scale (HAMA), as well as PASI response rate. Meanwhile, adverse events were evaluated during the whole clinical trial. Follow-up was carried out 30 days after treatment. RESULTS: There were 5 cases of shedding in this trial. In intention-to-treat analysis, 236 cases were included and each group contained 118 cases. On the 30th and 60th days, PASI scores of patients in each group were significantly lower than that at baseline (P<0.01) and the PASI score reduction of the treatment group was greater than that of the control group (P<0.01). Itch Rating Scale, DLQI, and HAMA scale were decreased in both groups after treatment, and the treatment group showed a better therapeutic effect (P<0.01). The response rates of PASI 50 and 75 were significantly higher than those in the control group [81.4% (96/118), 43.2% (51/118) vs. 41.5% (49/118), 11.0% (13/118), respectively, P<0.05]. During follow-up, the improvements in scores of PASI, Itch Rating Scale, DLQI, and HAMA of the treatment group were significantly greater than those of the control group (P<0.01). The response rates of PASI 50 and 75 in the treatment group were significantly higher than those in the control group, respectively (both P<0.05). No obvious adverse reaction was found in either group. CONCLUSION: ZMTM combined with Western medicines showed a better therapeutic effect in the treatment of psoriasis vulgaris without obvious adverse reaction. (Trial Registration No. ChiCTR-IOR-16008159).

Inspiratory muscle activation during inspiratory muscle training in patients with COPD.

BACKGROUND AND OBJECTIVES: The main target of inspiratory muscle training (IMT) is to improve diaphragm function in patients with COPD who have inspiratory muscle weakness. Ventilatory demand is already increased during quiet breathing in patients with COPD, and whether threshold load imposed by IMT would active more accessory muscle remained to be determined. The purpose of this study was to examine diaphragm and sternocleidomastoid (SCM) activation during IMT with intensities of 30% and 50% maximal inspiratory pressure (PImax). METHODS: Patients with COPD and a PImax lower than 60 cmH2O were recruited for the study. Surface electromyography (EMG) was used to measure diaphragm and SCM activation, and group-based trajectory modeling (GBTM) was used to identify activation patterns during IMT. The generalized estimating equation (GEE) was then used to detect differences of variables between various breathing tasks. Statistical significance was established at p < 0.05. RESULTS: A total of 30 patients with COPD participated in this study. All patients demonstrated significant increases in diaphragm and SCM activation during 30% and 50% PImax of IMT than during quiet breathing (all p < 0.001). Diaphragm demonstrated two distinct patterns in response to IMT: low activation (n = 8) and high activation (n = 22) group using GBTM analysis. CONCLUSION: Diaphragm and SCM were substantially activated during IMT in patients with COPD who had inspiratory muscle weakness. Regardless of whether diaphragm activation was high or low, SCM was activated to a greater extent in response to IMT.

A Meta-Analysis of the Association between Diabetes Mellitus and Traditional Chinese Medicine Constitution.

OBJECTIVE: To explore the distribution of constitution types of diabetes mellitus (DM) in traditional Chinese medicine (TCM) and to provide evidence-based medicine basis for the prevention and treatment of diabetes. METHODS: PubMed, Embase, Web of Science, and three Chinese databases were searched to include research literature on the relationship between diabetes and TCM constitution. The single rate study of cross-sectional literature was conducted with RStudio software, and the control meta-analysis of the diabetic and nondiabetic population was performed with Review Manager 5.3 software. Two independent reviewers assessed the methodological quality of the studies' data. The main outcomes included the distribution of constitutional types in the diabetic population and the odds ratio (OR) between the two. Effect sizes are expressed as proportions or ORs with 95% confidence intervals (CI). RESULTS: A total of 28,781 diabetic cases were included in 87 articles. Yin-deficiency, phlegm-dampness, and qi-deficiency accounted for 18% (95% CI (15%, 20%), P < 0.01), 17% (95% CI (15%, 19%), P < 0.01), and 13% (95% CI (11%, 15%), P < 0.01) of the total diabetic cases. The risk of diabetes in people with yin-deficiency and phlegm-dampness was 3.06 (95% CI (1.38-6.78), P=0.006) and 1.89 (95%CI (1.05-3.42), P=0.03) times higher than that in those with other constitutions, respectively. The distribution of TCM constitution of DM patients varied significantly in different regions and ages. CONCLUSION: Yin-deficiency and phlegm-dampness are the common constitution types of diabetic people, and they may also be the risk factors of diabetes. Balanced constitution may be a protective factor of diabetes. More high-quality cohort and case-control studies need to be designed to provide more valuable evidence-based basis for assessing the correlation between DM and TCM constitution.

The adjuvanticity of manganese for microbial vaccines via activating the IRF5 signaling pathway.

Manganese (Mn2+) has been reported to activate macrophages and NK cells, and to induce the production of type-I interferons (IFNs) by activating the cGAS-STING pathway. Few studies have been conducted on its adjuvanticity to microbial vaccines, and on the involvement of the interferon regulatory factor (IRF) 5 signaling pathway in the adjuvanticity. In this study, we demonstrated that Mn2+ could facilitate various microbial vaccines to induce enhanced antibody responses, and facilitate the influenza virus vaccine to induce protective immunity against the influenza virus challenge. When formulated in vaccines, Mn2+ could activate murine CD4+ T cells, CD8+ T cells, B cells and DCs, and induce the expression and phosphorylation of TANK-binding kinase 1 (TBK1) and IRF5 in the splenocytes of the immunized mice, resulting in the increased expression of type-I IFNs, TNF-α, B cell-activating factor of the TNF family (BAFF) and B lymphocyte-induced maturation protein-1 (Blimp-1). The induced TBK1 could recruit and bind the IRF5. Furthermore, the Mn2+ induced expression of IRF5 and Blimp-1 was prohibited by a IRF5 interfering oligonucleotide. The data suggest the Mn2+ could be used as a novel type of adjuvants for microbial vaccines, and the activation of IRF5 signaling pathway might involve in the adjuvanticity.

Anti-inflammatory effects of three withanolides isolated from Physalis angulata L. in LPS-activated RAW 264.7 cells through blocking NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Physalis angulata L. is commonly used in many countries as popular medicine for the treatment of a variety of diseases such as malaria, hepatitis, dermatitis and rheumatism. But the anti-inflammatory active constituents of this medicinal plant and their molecular mechanism are still not elucidated clearly. AIM OF THE STUDY: The aim of the study is to isolate and identify a series of compounds from the ethanolic extract of Physalis angulata L., and to investigate the anti-inflammatory activities in vitro and the molecular mechanism of physagulin A, physagulin C, and physagulin H. MATERIALS AND METHODS: In order to further understand the anti-inflammatory mechanism of the three compounds, their potential anti-inflammatory activities were investigated in vitro in LPS-activated RAW 264.7 macrophage cells by Griess assay, ELISA, Western blot and immunofluorescence methods in the present study. RESULTS: Physagulin A, physagulin C, and physagulin H could not only inhibit the release of NO, PGE2, IL-6 and TNF-α, but also could down-regulate the expression of iNOS and COX-2 proteins. Furthermore, physagulin A, physagulin C, and physagulin H could remarkably block the degradation of IκB-α and the nuclear translocation of NF-κB/p65 in LPS-activated RAW 264.7 cells. However, none of them could inhibit the phosphorylation of MAPKs family proteins ERK, JNK and p38. Thus, the anti-inflammatory actions of physagulin A, physagulin C, and physagulin H were mainly due to the significant inhibition of NF-κB signaling pathway rather than MAPKs signaling pathway. CONCLUSIONS: All the results clearly showed that physagulin A, physagulin C, and physagulin H demonstrated potent anti-inflammatory activity and can be used as novel NF-κB inhibitors. They are potential to be developed as an alternative or complementary agents for inflammatory diseases.

Total glucosides of paeony protects THP-1 macrophages against monosodium urate-induced inflammation via MALAT1/miR-876-5p/NLRP3 signaling cascade in gouty arthritis.

BACKGROUND: Monosodium urate (MSU)-mediated inflammatory response is a crucial inducing factor in gouty arthritis. Here, we explored the underlying mechanism of total glucosides of paeony (TGP) in MSU-induced inflammation of THP-1 macrophages in gouty arthritis. METHODS: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to detect cell viability. Enzyme-linked immunosorbent assay (ELISA) was utilized to measure the production of interleukin 1ß (IL-1ß) and tumor necrosis factor α (TNF-α). Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot assay were conducted to determine RNA and protein expression. Dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA pull down assay were used to confirm the interaction between miR-876-5p and MALAT1 or NLR family pyrin domain containing 3 (NLRP3). RESULTS: MSU-induced damage and inflammatory response in THP-1 macrophages were alleviated by the treatment of TGP in a dose-dependent manner. Overexpression of NLRP3 or MALAT1 reversed the protective effects of TGP in MSU-induced THP-1 macrophages. The binding relation between miR-876-5p and MALAT1 or NLRP3 was identified in THP-1 macrophages. MALAT1 up-regulated the expression of NLRP3 by sponging miR-876-5p in THP-1 macrophages. TGP suppressed MSU-induced inflammation in THP-1 macrophages through regulating MALAT1/miR-876-5p/NLRP3 axis. TGP suppressed MSU-induced activation of TLR4/MyD88/NF-κB pathway through regulating MALAT1/miR-876-5p/NLRP3 axis. CONCLUSION: In conclusion, TGP suppressed MSU-induced inflammation in THP-1 macrophages through regulating MALAT1/miR-876-5p/NLRP3 axis and TLR4/MyD88/NF-κB pathway, suggesting that TGP was a promising active ingredient for gouty arthritis treatment.

[Research progress of effect of berberine in treatment of ulcerative colitis based on cell signaling pathway].

Berberine is the main extract of Coptis chinensis, and its anti-inflammatory, antioxidant, antibacterial and immunomodulatory effects have been confirmed by modern studies. Ulcerative colitis(UC) is a chronic, idiopathic inflammatory bowel disease with unknown etiology. Its causes involve genetics, intestinal microecology and mucosal immune system disorders. In this paper, literatures on relevant pathways and mechanism of berberine on ulcerative colitis in recent years were consulted and summarized to provide me-thods and ideas for developing berberine in the treatment of UC and exploring the mechanisms. The results showed that berberine protects the intestinal mucosal barrier, restores the body's normal immune response, and improves oxidative stress by regulating multiple signaling pathways, such as JAK-STAT, NK-κB, PI3 K-AKT, MAPK, Nrf2, ERS, and MLCK-MLC, so as to treat UC.

Anti-inflammatory action of physalin A by blocking the activation of NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Physalis Calyx seu Fructus is typically used to treat inflammatory diseases such as upper respiratory tract infection and acute tonsillitis in clinical practice of China. Physalin A, a main active ingredient of this traditional Chinese medicine (TCM), has been reported for its significant anti-tumor activity. However, most reports focused on the studies of its anti-tumor activity, the anti-inflammatory activity of physalin A and its molecular mechanism are still not elucidated clearly. AIM OF THE STUDY: The aim of the study was to investigate the anti-inflammatory activities both in vitro and in vivo and molecular mechanism of physalin A. MATERIALS AND METHODS: The potential anti-inflammatory properties of physalin A were evaluated in vitro by lipopolysaccharide (LPS)-induced RAW 264.7 macrophage cells, and in vivo via two typical acute inflammation murine models. Some important inflammation-related molecules were analyzed by enzyme-linked immuno sorbent assay (ELISA) and Western blotting. RESULTS: The results showed that physalin A inhibited carrageenan-induced paw edema of rats and capillary permeability of mice induced by acetic acid in vivo. Furthermore, physalin A also significantly reduced the release of inflammatory mediators nitric oxide (NO), prostaglandin E2 (PGE2), and tumor necrosis factor-α (TNF-α) induced by lipopolysaccharide (LPS) in RAW 264.7 in vitro. Further investigations indicated that physalin A can down-regulate the high expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in a dose-dependent manner. Physalin A remarkably blocked the degradation of inhibitor of nuclear factor kappa B alpha (IκB-α) and the nuclear translocation of nuclear factor-κB (NF-κB) p65 induced by LPS in RAW 264.7 cells. However, physalin A did not significantly inhibit the phosphorylation of mitogen-activated protein kinases (MAPKs) family proteins c-Jun N-terminal kinase (JNK) or extracellular signal-regulated kinase (ERK) or p38. CONCLUSIONS: All the results clearly illustrated that the anti-inflammatory action of physalin A is due to the inactivation of NF-κB signal pathway, but is irrelevant to the MAPKs pathway.

Traditional Chinese Medicine guidelines for coronavirus disease 2019.

OBJECTIVE: To summarize the evidence from Traditional Chinese Medicine (TCM) practice in the treatment of coronavirus disease 2019 (COVID-19) and provide timely clinical practice guidance. METHODS: The guidelines were developed in accordance with the World Health Organization rapid guideline process. The evidence on TCM for COVID-19 from published guidelines, direct and indirect published clinical evidence, first hand clinical data, and expert experience and consensus were collected. The grading of recommendations assessment, development and evaluation (GRADE) method was used to grade the evidence and make the recommendations. RESULTS: Based on the available evidence, the guidelines recommended 17 Chinese medicines for COVID-19: 2 Chinese herbal granules, 7 Chinese patent medicines, and 8 Chinese herbal injections. CONCLUSION: As the literature search was conducted on March, any subsequent versions of these guidelines require an up-to-date literature review. We hope that the evidence summary in these will be helpful in global efforts to address COVID-19.

Treatment with Tang-luo-ning altered the microRNA expression profile in rats with diabetic peripheral neuropathy.

Tang-luo-ning (TLN) is a traditional Chinese herbal recipe that has been used to treat diabetic peripheral neuropathy (DPN); nevertheless, the underlying mechanism remains unclear. This study was aimed to investigate the microRNA (miRNA) expression profile in diabetic rats treated with TLN, and the target genes were predicted. Male Sprague-Dawley rats were randomly divided into control, diabetes, and TLN-treated diabetes groups. Diabetes was induced with streptozotocin, and TLN (5 g/kg/day) was orally given for eight weeks. Then, the sciatic nerves were harvested for miRNA microarray analyses. The differentially expressed miRNAs and their target genes were analyzed. Compared with the control rats, 24 miRNAs were significantly upregulated, and 59 were downregulated in the sciatic nerves of the diabetic rats by more than two folds (all P < 0.05). In TLN-treated diabetes rats, 26 miRNAs were upregulated, and 14 were downregulated compared with diabetic rats without TLN treatment (all P < 0.05). DPN-induced alterations of the miRNA profile were reversed by the TLN treatment. A total of 1402 target genes were screened. In GO analysis, genes in localization, cytoplasm, and protein binding processes were enriched, and the most significantly enriched pathways included the neurotrophin, Fc epsilon RI, and Wnt signaling pathways. Further analyses revealed that DVL1 and NTF3 genes were involved in these pathways. Our findings indicate that TLN may affect the Wnt and neurotrophin pathways by acting on DVL1 and NTF3 genes.

Clinical efficacy evaluation of a traditional Miao technique of crossbow needle therapy in the treatment of knee osteoarthritis: a multi-center randomized controlled trial.

BACKGROUND: Knee osteoarthritis (KOA) seriously reduces quality of life and is a major threat to the health of the middle-aged and elderly. This study aimed to assess the efficacy of Miao crossbow needle therapy vs. acupuncture for KOA therapy. METHODS: This multicenter, randomized controlled trial was performed at three hospitals between April 2016 and December 2016. The patients were randomized to receive crossbow needle (CN) or acupuncture (AT). All treatments were completed within 46 days. Evaluation of treatment was conducted on the 46th, 62nd, and 77th days. The primary endpoint was change of Western Ontario and McMaster Osteoarthritis Index (WOMAC) score on the 46th day. The secondary endpoints included WOMAC score, the Lysholm knee score, the Japanese Orthopedic Association (JOA) knee score, visual analog scale (VAS), and the MOS 36-item short-form health survey (SF-36), on the 46th, 62nd, and 77th day. RESULTS: Finally, data of 301 participants were analyzed for the efficacy of treatment. Compared with AT, there was a larger change of WOMAC score in the CN group after treatment [- 25.0 (95% CI - 27.0, - 23.0) vs. - 18.8 (95% CI - 20.8, - 16.9), P < 0.001]. In the CN group, the WOMAC score was lower at all three time points (P = 0.008, P = 0.003, P < 0.001 respectively), while the Lysholm knee score (P = 0.03) and JOA score (P = 0.013) were higher and the VAS score (P = 0.011) was lower on the 77th day. CONCLUSION: Both Miao crossbow needle therapy and acupuncture reduced the WOMAC score. Miao crossbow needle therapy can be an alternative method for treating patients with knee osteoarthritis. TRIAL REGISTRATION: ChiCTR, ChiCTR-INR-16008032. Registered on 12 March 2016.

Lycium barbarum Polysaccharide Extracted from Lycium barbarum Leaves Ameliorates Asthma in Mice by Reducing Inflammation and Modulating Gut Microbiota.

This study was designed to explore the impact of Lycium barbarum polysaccharide (LBP) on inflammation and gut microbiota in mice with allergic asthma. Mice were divided into four groups: control group, OVA (ovalbumin) group, Con+LBP group, OVA+LBP group. After 28 days of LBP intervention, mice were euthanized and associated indications were investigated. Histopathological examination demonstrated that LBP reduced lung injury. The results of our current study provide evidence that supplementation with LBP in asthmatic mice decreases TNF, IL-4, IL-6, MCP-1, and IL-17A in plasma and bronchoalveolar lavage fluid (BALF). Sequencing and analysis of gut microbiota indicated that compared with the OVA group, Lactobacillus and Bifidobacterium were increased, but Firmicutes, Actinobacteria, Alistipes, and Clostridiales were decreased in the OVA+LBP group. We also found that gut microbiota were related to inflammation-related factors. Therefore, we speculate that LBP may improve allergic asthma by altering gut microbiota and inhibiting inflammation in mice.